A series of novel flavonoid analogues were designed and synthesized. The aimed compounds for urease inhibitory activities were clearly superior to the control drug thiourea (more than 10 times). Among these compounds, L2 (IC50 = 1.343 ?M) and L12 (IC50 = 1.207 ?M) exhibited the most excellent urease inhibitory activity in vitro. The molecular dockings of L2, L12 and L22 into urease were performed to explore the binding modes and their structure-activity relationship. Furthermore, these aimed compounds showed good druggable properties.The treatment of diseases is under threat due to the increasing resistance of disease-causing bacteria to antibiotics. Likewise, free radical-induced oxidative stress has been implicated in several human disease conditions, such as cancer, stroke and diabetes. In the search for amino acid analogues with antibacterial and antioxidant properties as possible mimics of antimicrobial peptides, substituted N-(2'-nitrophenyl)pyrrolidine-2-carboxamides 4a-4k and N-(2'-nitrophenyl)piperidine-2-carboxamides 4l-4n have been synthesized via a two-step, one-pot amidation of the corresponding acids, using thionyl chloride with different amines in dichloromethane. The carboxamides were characterized by infrared and nuclear magnetic resonance spectroscopy, mass spectrometry and elemental analysis. Carboxamides 4a-4n were assayed against five Gram-positive and five Gram-negative bacterial strains using the broth micro-dilution procedure and compared to standard antibiotic drugs (streptomycin and nalidixic acid). 4b showed the highest antibacterial activity with a minimum inhibitory concentration (MIC) value of 15.6 ?g/mL against Staphylococcus aureus. Pertinently, 4b and 4k are promising candidates for narrow-spectrum (Gram-positive) and broad-spectrum antibiotics, respectively. The antioxidant properties of the carboxamides were also evaluated using the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical cation. 4a and 4k recorded the lowest IC50 values of 1.22 × 10-3 mg/mL (with DPPH) and 1.45 × 10-4 mg/mL (with ABTS), respectively. Notably, 4k recorded about 2.5 times better antioxidant capacity than the positive controls - ascorbic acid and butylated hydroxyanisole. These results bode well for N-aryl carboxamides as good mimics and substitutes for antimicrobial peptides towards mitigating bacterial resistance to antibiotics as well as ameliorating oxidative stress-related diseases.In the current study, a novel series of Schiff base derivatives of (E)-4-(benzylideneamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (3a-3f) and (E)-4-(benzylideneamino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide (3g-3q) were synthesize. The structures of synthetic compounds were elucidated by various spectroscopic techniques such as FTIR, NMR and spectrometric HRMS analysis. Synthetic derivatives were evaluated for their Jack Bean urease inhibitory activity using established in-vitro assay. It is worth mentioning here that most of our derivatives of both series displayed moderate to strong inhibitory activity, ranging between IC50 = 2.48 ± 0.78 ?M and 35.63 ± 1.26 ?M, as compared to standard thiourea (IC50 = 20.03 ± 2.03 ?M). Further, structure activity relationship studies suggest that the presence of halogen at ortho and para positions on the aryl ring in (E)-4-(benzylideneamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide derivatives and hydroxy and halogen in (E)-4-(benzylideneamino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide derivatives increased the urease inhibitory activity. Furthermore, molecular docking studies were carried out in order to investigate the binding mode of this class of compounds to urease. In order to evaluate drug likeness of compounds ADME evaluation was done, and the synthesized compounds were found to be non-toxic and present passive gastrointestinal absorption. The data suggests the synthesized sulphamethazine and sulphamethoxazole derivatives can serve as a novel scaffold to inhibit urease.Trypanosoma cruzi trypomastigotes adhere to extracellular matrix (ECM) to invade mammalian host cells regulating intracellular signaling pathways. Herein, resin-assisted enrichment of thiols combined with mass spectrometry were employed to map site-specific S-nitrosylated (SNO) proteins from T. cruzi trypomastigotes incubated (MTy) or not (Ty) with ECM. https://www.selleckchem.com/products/stemRegenin-1.html We confirmed the reduction of S-nitrosylation upon incubation with ECM, associated with a rewiring of the subcellular distribution and intracellular signaling pathways. Forty, 248 and 85 SNO-peptides were identified only in MTy, Ty or in both conditions, respectively. SNO proteins were enriched in ribosome, transport, carbohydrate and lipid metabolisms. Nitrosylation of histones H2B and H3 on Cys64 and Cys126, respectively, is described. Protein-protein interaction networks revealed ribosomal proteins, proteins involved in carbon and fatty acid metabolism to be among the enriched protein complexes. Kinases, phosphatases and enzymes involved in the metabolism oathways triggered in response to host interaction constitute potential diagnostic and therapeutic targets.In order to optimize sample preparation for shotgun proteomics, we compared four cysteine alkylating agents iodoacetamide, chloroacetamide, 4-vinylpyridine and methyl methanethiosulfonate, and estimated their effects on the results of proteome analysis. Because alkylation may result in methionine modification in vitro, proteomics data were searched for methionine to isothreonine conversions, which may mimic genomic methionine to threonine substitutions found in proteogenomic analyses. We found that chloroacetamide was superior to the other reagents in terms of the number of identified peptides and undesirable off-site reactions. Among the reagents evaluated, iodoacetamide increased the rate of methionine-to-isothreonine conversion, especially if the sample was prepared in gel. The presence of proline following methionine in a protein sequence increased the modification rate as well. Generally, the methionine-to-isothreonine conversion events were relatively rare, but should be taken into account in proteogenomic studies when searching for single nucleotide polymorphism events at the protein level.